3D Encapsulation, Bioprinting and Controlled Delivery of Functionally Engineered EVs (FEEs)

功能工程电动汽车 (FEE) 的 3D 封装、生物打印和受控交付

• 批准号: 10433850
• 负责人: LYNDON F COOPER
• 金额: $ 46.22万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-18 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10433850
• 关键词: 3-Dimensional; 3D Print; Activities of Daily Living; Address; Alginates; Anti-Inflammatory Agents; Architecture; Area; BMP2 gene; Binding; Biological Assay; Biological Models; Biology; Calvaria; Cartilage; Cells; Chronic; Complex; Cues; Defect; Dental; Development; Disease; Dose; Encapsulated; Engineering; Equilibrium; Event; Extracellular Matrix; Genes; Goals; Growth Factor; Health; Histology; Hybrids; Hydrogels; Immunology; Impairment; Individual; Inflammasome; Inflammation; Inflammatory; Injury; Ink; Kinetics; Knowledge; Laboratories; MADH7 gene; MMP2 gene; Measurement; Mediator of activation protein; Mesenchymal Stem Cells; MicroRNAs; Modeling; Muscle; Musculoskeletal; Musculoskeletal System; Natural regeneration; Nerve; Pathway interactions; Peptides; Play; Polymers; Process; Production; Property; Rattus; Regenerative Medicine; Regenerative pathway; Reporter; Role; Signal Transduction; Site; Structure; System; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Work; base; bioprinting; body system; clinical translation; controlled release; craniofacial; craniofacial tissue; crosslink; cytokine; extracellular vesicles; immunoregulation; improved; in vivo; macrophage; monomer; novel strategies; paracrine; precision medicine; prevent; protein expression; recruit; regenerative; repaired; scaffold; spatiotemporal; stem cell exosomes; stem cell growth; stem cell therapy; tissue injury; tissue regeneration; tissue repair; tool

Summary: Tissue repair is a complex process that involves a delicate temporal balance between inflammatory and regenerative mechanisms. In health, initial inflammatory events are replaced by regenerative processes in a coordinated manner. This sequence is disrupted in diseased states and complex injuries. The goal of regenerative medicine is to reestablish this balance by preventing chronic/aberrant inflammation and promoting repair and regeneration in a tissue-specific manner. While stem cell and growth factor therapies have been explored for this purpose traditionally, recent studies highlight the immunomodulatory and protective functions of mesenchymal stem cell derived extracellular vesicles (MSC EVs). Although MSC EVs possess versatile properties, to engage tissue-specific pathways and fit the goals of precision medicine with translational relevance, MSC EVs have to be engineered for enhanced pathway-specific functionality and delivered on site in a spatially and temporally controlled manner. In this proposal, leveraging our preliminary results and our expertise in EV biology, immunology and bone biology, we hypothesize that: Spatiotemporal control of immunomodulatory and regenerative pathways can be achieved by selective incorporation of Functionally Engineered EVs (FEEs)in 3D printed scaffolds. Using bone regeneration as a model system, we will test this hypothesis in three specific aims. In aim 1, we will generate functionally engineered EVs (FEEs) that target specific osteoinductive and immunomodulatory pathways. In aim 2, we will develop a photocrosslinkable alginate-based delivery system with EV carrier and release motifs for spatial localization and temporally controlled delivery of the FEEs developed in aim 1. In aim 3, we will utilize 3D printing technology to print defined structures encapsulating the FEEs for spatially and temporally controlled biphasic delivery in vivo. This system will be tested in a rat calvarial defect model. From the proposed studies, we will develop a platform technology that can impact the field of regenerative medicine beyond the craniofacial and musculoskeletal systems.

概括： 组织修复是一个复杂的过程，涉及炎症和炎症之间微妙的时间平衡。 再生机制。在健康方面，最初的炎症事件被再生过程所取代 协调一致的方式。该序列在疾病状态和复杂损伤中被破坏。目标是 再生医学是通过预防慢性/异常炎症和促进 以组织特异性方式修复和再生。虽然干细胞和生长因子疗法已 传统上为此目的进行了探索，最近的研究强调了免疫调节和保护功能 间充质干细胞衍生的细胞外囊泡（MSC EV）。尽管 MSC EV 具有多功能性 特性，以参与组织特异性途径并通过转化来满足精准医学的目标 相关性，MSC EV 必须经过设计以增强特定路径的功能并在现场交付 以空间和时间受控的方式。在本提案中，利用我们的初步结果和我们的 在 EV 生物学、免疫学和骨生物学方面的专业知识，我们假设： 免疫调节和再生途径可以通过选择性掺入功能性物质来实现 3D 打印支架中的工程电动汽车 (FEE)。使用骨再生作为模型系统，我们将对此进行测试 三个具体目标的假设。在目标 1 中，我们将生产功能工程电动汽车 (FEE)，其目标是 特定的骨诱导和免疫调节途径。在目标 2 中，我们将开发一种可光交联的 基于藻酸盐的递送系统，具有 EV 载体和释放基序，用于空间定位和时间定位 目标 1 中开发的费用的受控交付。在目标 3 中，我们将利用 3D 打印技术来打印 定义的结构封装了 FEE，用于体内空间和时间控制的双相递送。这 系统将在大鼠颅骨缺损模型中进行测试。根据拟议的研究，我们将开发一个平台 可以影响颅面和肌肉骨骼以外的再生医学领域的技术 系统。